Nature Microbiology最新文献_第3页

Superinfection promotes replication and diversification of defective HIV-1 proviruses in people with non-suppressible viraemia. 在非抑制性病毒血症患者中，重复感染促进有缺陷的HIV-1原病毒的复制和多样化。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-10-03 DOI: 10.1038/s41564-025-02135-z

Vivek Hariharan,Jennifer A White,Filippo Dragoni,Emily J Fray,Nicholas Pathoulas,Milica Moskovljevic,Hao Zhang,Anushka Singhal,Jun Lai,Subul A Beg,Eileen P Scully,Elizabeth A Gilliams,David S Block,Jeanne Keruly,Richard D Moore,Janet D Siliciano,Francesco R Simonetti,Robert F Siliciano

{"title":"Superinfection promotes replication and diversification of defective HIV-1 proviruses in people with non-suppressible viraemia.","authors":"Vivek Hariharan,Jennifer A White,Filippo Dragoni,Emily J Fray,Nicholas Pathoulas,Milica Moskovljevic,Hao Zhang,Anushka Singhal,Jun Lai,Subul A Beg,Eileen P Scully,Elizabeth A Gilliams,David S Block,Jeanne Keruly,Richard D Moore,Janet D Siliciano,Francesco R Simonetti,Robert F Siliciano","doi":"10.1038/s41564-025-02135-z","DOIUrl":"https://doi.org/10.1038/s41564-025-02135-z","url":null,"abstract":"During replication of some RNA viruses, defective particles can spontaneously arise and interfere with wild-type (WT) virus replication. However, these defective interfering particles (DIPs) have not been reported in people with HIV-1 (PWH). Here we find DIPs in PWH who have a rare, polyclonal form of non-suppressible viraemia (NSV). We characterized the source of NSV in two PWH who never reached undetectable viral load despite adherence to antiretroviral therapy (ART). Remarkably, in each participant, we found a diverse set of defective viral genomes sharing the same fatal deletions. This paradoxical accumulation of mutations by viruses with fatal defects was driven by superinfection with intact viruses, resulting in mobilization of defective genomes and accumulation of additional mutations during untreated infection. These defective proviruses interfere with WT virus replication, conditionally replicate and, in one case, have an R0 > 1, enabling in vivo spread. Despite this, clinical outcomes showed no beneficial effect of these DIPs. These findings demonstrate that fatally defective proviruses, traditionally considered evolutionary dead ends, can replicate and diversify upon superinfection without preventing disease progression.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"69 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and artificial intelligence-guided mechanistic elucidation of a narrow-spectrum antibiotic. 窄谱抗生素的发现和人工智能引导下的机制阐释。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-10-03 DOI: 10.1038/s41564-025-02142-0

Denise B Catacutan,Vian Tran,Autumn Arnold,Jeremie Alexander,Gabriele Corso,Yeganeh Yousefi,Megan M Tu,Stewart McLellan,Dominique Tertigas,Jakob Magolan,Michael G Surette,Eric D Brown,Brian K Coombes,Regina Barzilay,Jonathan M Stokes

{"title":"Discovery and artificial intelligence-guided mechanistic elucidation of a narrow-spectrum antibiotic.","authors":"Denise B Catacutan,Vian Tran,Autumn Arnold,Jeremie Alexander,Gabriele Corso,Yeganeh Yousefi,Megan M Tu,Stewart McLellan,Dominique Tertigas,Jakob Magolan,Michael G Surette,Eric D Brown,Brian K Coombes,Regina Barzilay,Jonathan M Stokes","doi":"10.1038/s41564-025-02142-0","DOIUrl":"https://doi.org/10.1038/s41564-025-02142-0","url":null,"abstract":"Current clinical antibiotics are largely broad-spectrum agents that can alter the gut microbiome and promote colonization by Enterobacteriaceae, which are often drug resistant. This includes adherent-invasive Escherichia coli (AIEC), particularly in patients with inflammatory bowel disease, in which dysbiosis creates a niche for this pathogen to colonize. There is an urgent and unmet need for novel narrow-spectrum and microbiome-sparing antibiotics. Here we screened 10,747 bioactive small molecules for antibacterial activity against AIEC and discovered enterololin, an antibacterial compound with targeted activity against Enterobacteriaceae species. Enterololin could overcome intrinsic and acquired resistance mechanisms in clinical isolates when combined with a subinhibitory concentration of SPR741, a polymyxin B analogue used here to increase outer membrane permeability in Gram-negative bacteria. Molecular substructure- and deep learning-guided mechanism-of-action investigations revealed that enterololin perturbs lipoprotein trafficking through a mechanism involving the LolCDE complex, laboratory-evolved resistant mutants predominantly mapped to lolC and lolE, with an in vitro frequency of resistance of ~10-8 to 10-7. Enterololin showed low mammalian cytotoxicity (HEK293 half-maximal inhibitory concentration ~100 µg ml-1) and suppressed AIEC infection in mouse models when administered in combination with SPR741, while largely preserving the overall microbiome composition. This study highlights the utility of deep learning methods for predicting molecular interactions and identifies a promising Enterobacteriaceae-specific antibacterial candidate for further development.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"111 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Publisher Correction: Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections. 出版商更正：合理设计医院特异性噬菌体鸡尾酒治疗阴沟肠杆菌复合感染。

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-10-01 DOI: 10.1038/s41564-025-02163-9

Dinesh Subedi, Fernando Gordillo Altamirano, Rylee Deehan, Avindya Perera, Ruzeen Patwa, Xenia Kostoulias, Denis Korneev, Luke Blakeway, Nenad Macesic, Anton Y Peleg, Jeremy J Barr

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Structure of a distinct β-barrel assembly machinery complex in the Bacteroidota. 拟杆菌科中一个独特的β-桶组装机械复合体的结构。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-10-01 DOI: 10.1038/s41564-025-02132-2

Augustinas Silale,Mariusz Madej,Katarzyna Mikruta,Andrew M Frey,Adam J Hart,Arnaud Baslé,Carsten Scavenius,Jan J Enghild,Matthias Trost,Robert P Hirt,Bert van den Berg

{"title":"Structure of a distinct β-barrel assembly machinery complex in the Bacteroidota.","authors":"Augustinas Silale,Mariusz Madej,Katarzyna Mikruta,Andrew M Frey,Adam J Hart,Arnaud Baslé,Carsten Scavenius,Jan J Enghild,Matthias Trost,Robert P Hirt,Bert van den Berg","doi":"10.1038/s41564-025-02132-2","DOIUrl":"https://doi.org/10.1038/s41564-025-02132-2","url":null,"abstract":"The Gram-negative β-barrel assembly machinery (BAM) complex catalyses the folding and membrane insertion of newly synthesized β-barrel outer membrane proteins. The BAM is structurally conserved, but most studies have focused on Gammaproteobacteria. Here, using single-particle cryogenic electron microscopy, quantitative proteomics and functional assays, we show that the BAM complex is distinct within the Bacteroidota. Cryogenic electron microscopy structures of BAM complexes from the human gut symbiont Bacteroides thetaiotaomicron (3.3 Å) and the human oral pathogen Porphyromonas gingivalis (3.2 Å) show similar, seven-component complexes of ~325 kDa. The complexes are mostly extracellular and comprise canonical BamA and BamD; an integral, essential outer membrane protein, BamG, that associates with BamA; and four surface-exposed lipoproteins: BamH-K. Absent from the BAM in Pseudomonadota, BamG-K form a large, extracellular dome that may confer additional functionality to enable the folding and assembly of β-barrel-surface-exposed lipoprotein complexes that are a hallmark of the Bacteroidota. Our findings develop our understanding of fundamental biological processes in an important bacterial phylum.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"99 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Why editors go to conferences 编辑为什么要参加会议

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-10-01 DOI: 10.1038/s41564-025-02151-z

引用次数: 0

How nutrient starvation impacts the gut microbiome. 营养缺乏如何影响肠道微生物群。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-09-30 DOI: 10.1038/s41564-025-02139-9

Sylvie Estrela,Jonathan Z Long,Kerwyn Casey Huang

引用次数: 0

Polymyxin B lethality requires energy-dependent outer membrane disruption. 多粘菌素B的致死率需要能量依赖性外膜破坏。

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-09-29 DOI: 10.1038/s41564-025-02133-1

Carolina Borrelli, Edward J A Douglas, Sophia M A Riley, Aikaterini Ellas Lemonidi, Gerald Larrouy-Maumus, Wen-Jung Lu, Boyan B Bonev, Andrew M Edwards, Bart W Hoogenboom

{"title":"Polymyxin B lethality requires energy-dependent outer membrane disruption.","authors":"Carolina Borrelli, Edward J A Douglas, Sophia M A Riley, Aikaterini Ellas Lemonidi, Gerald Larrouy-Maumus, Wen-Jung Lu, Boyan B Bonev, Andrew M Edwards, Bart W Hoogenboom","doi":"10.1038/s41564-025-02133-1","DOIUrl":"10.1038/s41564-025-02133-1","url":null,"abstract":"<p><p>Polymyxin antibiotics target lipopolysaccharides (LPSs) in both membranes of the bacterial cell envelope, leading to bacterial killing through a poorly defined mechanism. Here we demonstrate that metabolic activity is essential for the lethality of clinically relevant doses of polymyxin B (PmB) and leverage this insight to determine its mode of action. PmB killed exponential-phase Escherichia coli but did not eliminate stationary-phase cells unless a carbon source was available. Antibiotic lethality correlated with surface protrusions visible by atomic force microscopy and LPS loss from the outer membrane via processes that required LPS synthesis and transport but that were blocked by the MCR-1 polymyxin resistance determinant. While energy-dependent outer-membrane disruption was not directly lethal, it facilitated PmB access to the inner membrane, which the antibiotic permeabilized in an energy-independent manner, leading to cell death. This work reveals how metabolic inactivity confers tolerance of an important, membrane-targeting antibiotic.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identified receptors shed light on Epstein-Barr virus infection. 鉴定出的受体为爱泼斯坦-巴尔病毒感染提供了线索。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-09-29 DOI: 10.1038/s41564-025-02123-3

Shanchuan Liu,Alexander S Hahn

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Epstein-Barr virus exploits desmocollin 2 as the principal epithelial cell entry receptor. 爱泼斯坦-巴尔病毒利用桥蛋白2作为主要的上皮细胞进入受体。

IF 28.3 1区生物学

Nature Microbiology Pub Date : 2025-09-26 DOI: 10.1038/s41564-025-02126-0

Hongbo Wang,Zongjun Mou,Yao Yu Yeo,Qianyun Ge,Xiang Liu,Yohei Narita,Zhixuan Li,Chong Wang,Wanyu Li,Katelyn Rs Zhao,Jenny Li,Wei Bu,Benjamin Gewurz,Jeffrey I Cohen,Mingxiang Teng,Xinghong Dai,Xuefeng Liu,Sizun Jiang,Bo Zhao

{"title":"Epstein-Barr virus exploits desmocollin 2 as the principal epithelial cell entry receptor.","authors":"Hongbo Wang,Zongjun Mou,Yao Yu Yeo,Qianyun Ge,Xiang Liu,Yohei Narita,Zhixuan Li,Chong Wang,Wanyu Li,Katelyn Rs Zhao,Jenny Li,Wei Bu,Benjamin Gewurz,Jeffrey I Cohen,Mingxiang Teng,Xinghong Dai,Xuefeng Liu,Sizun Jiang,Bo Zhao","doi":"10.1038/s41564-025-02126-0","DOIUrl":"https://doi.org/10.1038/s41564-025-02126-0","url":null,"abstract":"Epstein-Barr virus (EBV) infects B and epithelial cells, causing various lymphomas and epithelial malignancies. Although cell-free infection of epithelial cells is inefficient, direct B-epithelial cell contact infection is highly efficient and probably the dominant route. To identify mechanisms of contact-mediated infection, we implemented a genome-wide CRISPR screen and uncovered desmocollin 2 (DSC2) as an EBV epithelial receptor and DSC3 as a co-factor for infection. DSC2 and DSC3 double knockout significantly inhibited both cell-free and cell-cell contact EBV infection of normal oral keratinocytes, while their overexpression permitted infection in receptor-negative cells. Antibodies to DSC2 blocked infection across normal oral keratinocytes, primary oral keratinocytes, and head and neck epithelial organoids. Combining DSC2 and DSC3 antibodies efficiently blocked cell-cell contact infection. Mechanistically, DSC2 interacted with the EBV gH/gL glycoprotein and facilitated epithelial fusion. Notably, EphA2 overexpression failed to restore infection in DSC2/3-deficient cells, indicating its dependence on DSC2/3. Our findings establish DSC2 as a principal EBV entry receptor and target for vaccine and therapeutic development.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"102 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A roadmap for equitable reuse of public microbiome data 公平重用公共微生物组数据的路线图。

IF 19.4 1区生物学

Nature Microbiology Pub Date : 2025-09-26 DOI: 10.1038/s41564-025-02116-2

Laura A. Hug, Roland Hatzenpichler, Cristina Moraru, André R. Soares, Folker Meyer, Anke Heyder, The Data Reuse Consortium, Alexander J. Probst

{"title":"A roadmap for equitable reuse of public microbiome data","authors":"Laura A. Hug, Roland Hatzenpichler, Cristina Moraru, André R. Soares, Folker Meyer, Anke Heyder, The Data Reuse Consortium, Alexander J. Probst","doi":"10.1038/s41564-025-02116-2","DOIUrl":"10.1038/s41564-025-02116-2","url":null,"abstract":"Science benefits from rapid open data sharing, but current guidelines for data reuse were established two decades ago, when databases were several million times smaller than they are today. These guidelines are largely unfamiliar to the scientific community, and, owing to the rapid increase in biological data generated in the past decade, they are also outdated. As a result, there is a lack of community standards suited to the current landscape and inconsistent implementation of data sharing policies across institutions. Here we discuss current sequence data sharing policies and their benefits and drawbacks, and present a roadmap to establish guidelines for equitable sequence data reuse, developed in consultation with a data consortium of 167 microbiome scientists. We propose the use of a Data Reuse Information (DRI) tag for public sequence data, which will be associated with at least one Open Researcher and Contributor ID (ORCID) account. The machine-readable DRI tag indicates that the data creators prefer to be contacted before data reuse, and simultaneously provides data consumers with a mechanism to get in touch with the data creators. The DRI aims to facilitate and foster collaborations, and serve as a guideline that can be expanded to other data types. In this Consensus Statement, a consortium of microbiome scientists discuss current sequencing data sharing policies and propose the use of a Data Reuse Information (DRI) tag to promote equitable and collaborative data sharing.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"10 10","pages":"2384-2395"},"PeriodicalIF":19.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41564-025-02116-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0